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Personalized Medicine in Neurological and Neurosurgical Diseases

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A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Personalized Therapy and Drug Delivery".

Deadline for manuscript submissions: closed (25 July 2023) | Viewed by 21453

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Special Issue Editors

Dr. Lu-Ting Kuo

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Guest Editor

Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei 100, Taiwan
Interests: neuro-oncology; treatment for hydrocephalus; spine surgery; neurotraumatology; molecular neurology

Dr. Abel Po-Hao Huang

E-Mail Website
Guest Editor

Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan
Interests: clincial neurosurgery; regenerative medicine; biomedical engineering; medical device; clinical trial

Special Issue Information

Dear Colleagues,

The worldwide prevalence of neurological and neurosurgical diseases is growing on an epidemic scale. The early detection and prompt treatment of these diseases are essential for improving functional outcomes and decreasing economic health burdens. For this, modern molecular, biochemical, pathophysiological, and equipment studies are required, enabling a personalized approach to the choice of treatment.

Personalized medicine includes a range of approaches to health care based on factual data: from precise molecular diagnostics, to predicting the onset or development of a disease on the basis of “omics”, to personalized treatment and monitoring.

We are pleased to invite you to submit papers detailing the results of translational research on neurological and neurosurgical diseases aimed at improving the prevention, diagnosis, risk assessment, and treatment of neurological and neurosurgical diseases from the standpoint of personalized medicine.

This Special Issue aims to familiarize physicians and researchers with the latest advances in the translational research of neurological and neurosurgical diseases from the standpoint of personalized medicine.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but not limited to) the following:

Personalized medicine in brain metastasis;
Personalized medicine in glioblastomas;
Personalized medicine in meningiomas;
Personalized medicine in pituitary tumors;
Personalized medicine in radio-oncology treatment of brain tumors;
Personalized medicine in traumatic brain injury;
Personalized medicine in intracerebral hemorrhage;
Personalized medicine in stroke treatment
Advanced neuro-imaging in neurological and neurosurgical diseases
Connectomics in neurological and neurosurgical diseases
Genomics, GWAS, and population genetics of neurological and neurosurgical diseases;
Epigenetics and microRNAs of neurological and neurosurgical diseases;
Proteomic of neurological and neurosurgical diseases;
Inflammation in neurological and neurosurgical diseases;
Oxidative stress in neurological and neurosurgical disease;
Immunology in neurological and neurosurgical diseases.

We look forward to receiving your contributions.

Dr. Lu-Ting Kuo
Dr. Abel Po-Hao Huang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

personalized medicine
neurosurgery
neurology
brain tumor
neuro-imaging
traumatic brain injury
intracerebral hemorrhage
stroke
genetic
epigenetic
connectomics

Published Papers (9 papers)

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Research

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15 pages, 1738 KiB

Open AccessFeature PaperArticle

Variations in Theta/Beta Ratio and Cognitive Performance in Subpopulations of Subjects with ADHD Symptoms: Towards Neuropsychological Profiling for Patient Subgrouping

by Wendy Verónica Herrera-Morales, Julián Valeriano Reyes-López, Karen Nicte-Ha Tuz-Castellanos, Desiree Ortegón-Abud, Leticia Ramírez-Lugo, Efraín Santiago-Rodríguez and Luis Núñez-Jaramillo

J. Pers. Med. 2023, 13(9), 1361; https://doi.org/10.3390/jpm13091361 - 07 Sep 2023

Viewed by 1817

Abstract

ADHD is a neurodevelopmental disorder appearing in childhood but remaining in many cases in adults. There are both pharmacological and non-pharmacological approaches to treating ADHD, but they do not have the same efficacy in all subjects. Better knowledge of the neurophysiological basis of this disorder will allow for the design of more effective treatments. Studies performing qEEG analysis in children suggest the existence of subgroups of ADHD patients with different neurophysiological traits. There are fewer studies in adults, who might have undergone plastic changes allowing them to cope with ADHD symptoms along with brain maturation. Herein, we study cognitive performance and the theta/beta ratio in young adults with ADHD symptoms. We found that subjects with ADHD symptoms and low working memory performance (n = 30) present higher theta/beta ratios than controls (n = 40) at O2 and T6 in the eyes-closed condition, as well as a tendency toward a higher theta/beta ratio at O1 and Cz. Subjects with ADHD and high working memory performance (n = 50) do not differ from the controls in their theta/beta ratios at any derivation. Our results suggest that neuropsychological profiling could be useful for patient subgrouping. Further research will allow for the distinction of neuropsychological profiles and their neurophysiological correlates, leading to a better classification of ADHD subtypes, thus improving treatment selection. Full article

(This article belongs to the Special Issue Personalized Medicine in Neurological and Neurosurgical Diseases)

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10 pages, 811 KiB

Open AccessArticle

Analysis of Mortality in Intracerebral Hemorrhage Patients with Hyperacute Ischemic Stroke Treated Using Thrombolytic Therapy: A Nationwide Population-based Cohort Study in South Korea

by Hyun-Young Choi, Yongil Cho, Wonhee Kim, Yang-Ki Minn, Gu-Hyun Kang, Yong-Soo Jang, Yoonje Lee, Jae-Guk Kim, Jihoon Kim, Youngsuk Cho, Hyungoo Shin, Shinje Moon, Chiwon Ahn, Juncheol Lee, Dong-Geum Shin and Jae-Keun Park

J. Pers. Med. 2022, 12(8), 1260; https://doi.org/10.3390/jpm12081260 - 30 Jul 2022

Cited by 3 | Viewed by 1591

Abstract

This study investigated the impact of intracerebral hemorrhage (ICH) on the cumulative mortality of patients with hyperacute ischemic stroke. This population-based retrospective cohort study used claims data from the National Health Insurance Service customized database of South Korea. The recruitment period was 2005–2018. The study population included patients with hyperacute ischemic stroke who had received intravenous thrombolysis. The primary endpoint was 12-month cumulative mortality, which was analyzed in both the ICH and no-ICH groups. Of the 50,550 patients included, 2567 (5.1%) and 47,983 (94.9%) belonged to the ICH and no-ICH groups, respectively. In the univariable analysis for 12-month mortality, ICH patients were substantially more prevalent among dead patients than among patients who survived (11.6% versus 3.6%; p < 0.001). The overall 12-month cumulative mortality rate was 18.8%. Mortality in the ICH group was higher than that in the no-ICH group (42.8% versus 17.5%; p < 0.001). In the multivariable analysis, the risk of 12-month cumulative mortality was 2.97 times higher in the ICH group than in the no-ICH group (95% confidence interval, 2.79–3.16). The risk of 12-month cumulative mortality in hyperacute ischemic stroke can increase approximately threefold after the occurrence of spontaneous ICH following intravenous thrombolysis. Full article

(This article belongs to the Special Issue Personalized Medicine in Neurological and Neurosurgical Diseases)

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11 pages, 1303 KiB

Open AccessArticle

Automatic and Efficient Prediction of Hematoma Expansion in Patients with Hypertensive Intracerebral Hemorrhage Using Deep Learning Based on CT Images

by Chao Ma, Liyang Wang, Chuntian Gao, Dongkang Liu, Kaiyuan Yang, Zhe Meng, Shikai Liang, Yupeng Zhang and Guihuai Wang

J. Pers. Med. 2022, 12(5), 779; https://doi.org/10.3390/jpm12050779 - 12 May 2022

Cited by 7 | Viewed by 1868

Abstract

Patients with hypertensive intracerebral hemorrhage (ICH) have a high hematoma expansion (HE) incidence. Noninvasive prediction HE helps doctors take effective measures to prevent accidents. This study retrospectively analyzed 253 cases of hypertensive intraparenchymal hematoma. Baseline non-contrast-enhanced CT scans (NECTs) were collected at admission and compared with subsequent CTs to determine the presence of HE. An end-to-end deep learning method based on CT was proposed to automatically segment the hematoma region, region of interest (ROI) feature extraction, and HE prediction. A variety of algorithms were employed for comparison. U-Net with attention performs best in the task of segmenting hematomas, with the mean Intersection overUnion (mIoU) of 0.9025. ResNet-34 achieves the most robust generalization capability in HE prediction, with an area under the receiver operating characteristic curve (AUC) of 0.9267, an accuracy of 0.8827, and an F₁ score of 0.8644. The proposed method is superior to other mainstream models, which will facilitate accurate, efficient, and automated HE prediction. Full article

(This article belongs to the Special Issue Personalized Medicine in Neurological and Neurosurgical Diseases)

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12 pages, 436 KiB

Open AccessArticle

Comparison of Nine Early Warning Scores for Identification of Short-Term Mortality in Acute Neurological Disease in Emergency Department

by Carlos Durantez-Fernández, Begoña Polonio-López, José L. Martín-Conty, Clara Maestre-Miquel, Antonio Viñuela, Raúl López-Izquierdo, Laura Mordillo-Mateos, Cristina Jorge-Soto, Martín Otero-Agra, Michele Dileone, Joseba Rabanales-Sotos and Francisco Martín-Rodríguez

J. Pers. Med. 2022, 12(4), 630; https://doi.org/10.3390/jpm12040630 - 14 Apr 2022

Cited by 3 | Viewed by 1773

Abstract

(1) Background: The aim was screening the performance of nine Early Warning Scores (EWS), to identify patients at high-risk of premature impairment and to detect intensive care unit (ICU) admissions, as well as to track the 2-, 7-, 14-, and 28-day mortality in a cohort of patients diagnosed with an acute neurological condition. (2) Methods: We conducted a prospective, longitudinal, observational study, calculating the EWS [Modified Early Warning Score (MEWS), National Early Warning Score (NEWS), VitalPAC Early Warning Score (ViEWS), Modified Rapid Emergency Medicine Score (MREMS), Early Warning Score (EWS), Hamilton Early Warning Score (HEWS), Standardised Early Warning Score (SEWS), WHO Prognostic Scored System (WPSS), and Rapid Acute Physiology Score (RAPS)] upon the arrival of patients to the emergency department. (3) Results: In all, 1160 patients were included: 808 patients were hospitalized, 199 cases (17%) required ICU care, and 6% of patients died (64 cases) within 2 days, which rose to 16% (183 cases) within 28 days. The highest area under the curve for predicting the need for ICU admissions was obtained by RAPS and MEWS. For predicting mortality, MREMS obtained the best scores for 2- and 28-day mortality. (4) Conclusions: This is the first study to explore whether several EWS accurately identify the risk of ICU admissions and mortality, at different time points, in patients with acute neurological disorders. Every score analyzed obtained good results, but it is suggested that the use of RAPS, MEWS, and MREMS should be preferred in the acute setting, for patients with neurological impairment. Full article

(This article belongs to the Special Issue Personalized Medicine in Neurological and Neurosurgical Diseases)

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12 pages, 11368 KiB

Open AccessArticle

4-Hydroxyphenyllactic Acid in Cerebrospinal Fluid as a Possible Marker of Post-Neurosurgical Meningitis: Retrospective Study

by Alisa K. Pautova, Anastasiia Yu. Meglei, Ekaterina A. Chernevskaya, Irina A. Alexandrova and Natalia V. Beloborodova

J. Pers. Med. 2022, 12(3), 399; https://doi.org/10.3390/jpm12030399 - 04 Mar 2022

Cited by 3 | Viewed by 2242

Abstract

The search for new potential biomarkers for the diagnostics of post-neurosurgical bacterial meningitis is required because of the difficulties in its early verification using results of the routine laboratory and biochemical analyses of the cerebrospinal fluid (CSF). The goal of the study was to determine the contents of the aromatic metabolites and biomarkers in the CSF samples of the post-neurosurgical patients (n = 82) and their potential diagnostical significance for the evaluation of the risk of post-neurosurgical meningitis. Patients with signs of post-neurosurgical meningitis (n = 30) had lower median values of glucose and higher values of cell count, neutrophils, lactate, protein, 3-(4-hydroxyphenyl)lactic acid (p-HPhLA), and interleukin-6 (IL-6) than patients without signs of post-neurosurgical meningitis (n = 52). ROC analysis for IL-6 and p-HPhLA resulted in 0.785 and 0.734 values of the area under the ROC curve, with sensitivity 96.30 and 66.67%; specificity 54.17 and 82.69%, respectively. IL-6 should be considered as a non-specific biomarker, in contrast to the microbial metabolite p-HPhLA. If the concentration of p-HPhLA was more or equal to 0.9 µmol/L, the risk of bacterial complications was 9.6 times higher. p-HPhLA is a promising marker for the prognosis of post-neurosurgical meningitis, and its determination on a larger group of post-neurosurgical patients can subsequently prove its diagnostic significance for the verification of CNS infections. Full article

(This article belongs to the Special Issue Personalized Medicine in Neurological and Neurosurgical Diseases)

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Review

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12 pages, 297 KiB

Open AccessReview

Application of Pupillometry in Neurocritical Patients

by Chiu-Hao Hsu and Lu-Ting Kuo

J. Pers. Med. 2023, 13(7), 1100; https://doi.org/10.3390/jpm13071100 - 05 Jul 2023

Cited by 1 | Viewed by 1440

Abstract

Pupillary light reflex (PLR) assessment is a crucial examination for evaluating brainstem function, particularly in patients with acute brain injury and neurosurgical conditions. The PLR is controlled by neural pathways modulated by both the sympathetic and parasympathetic nervous systems. Altered PLR is a strong predictor of adverse outcomes after traumatic and ischemic brain injuries. However, the assessment of PLR needs to take many factors into account since it can be modulated by various medications, alcohol consumption, and neurodegenerative diseases. The development of devices capable of measuring pupil size and assessing PLR quantitatively has revolutionized the non-invasive neurological examination. Automated pupillometry, which is more accurate and precise, is widely used in diverse clinical situations. This review presents our current understanding of the anatomical and physiological basis of the PLR and the application of automated pupillometry in managing neurocritical patients. We also discuss new technologies that are being developed, such as smartphone-based pupillometry devices, which are particularly beneficial in low-resource settings. Full article

(This article belongs to the Special Issue Personalized Medicine in Neurological and Neurosurgical Diseases)

24 pages, 393 KiB

Open AccessReview

Orphan Drugs in Neurology—A Narrative Review

by Carmen Adella Sirbu, Raluca Ivan, Francois Jerome Authier, Florentina Ionita-Radu, Dragos Catalin Jianu, Octavian Vasiliu, Ciprian Constantin and Sorin Tuță

J. Pers. Med. 2023, 13(3), 420; https://doi.org/10.3390/jpm13030420 - 26 Feb 2023

Viewed by 1968

Abstract

Background and aims: Orphan diseases, or rare diseases, are defined in Europe as diseases that affect less than 5 out of every 10,000 citizens. Given the small number of cases and the lack of profit potential, pharmaceutical companies have not invested much in the development of possible treatments. However, over the last few years, new therapies for rare diseases have emerged, giving physicians a chance to offer personalized treatment. With this paper, we aim to present some of the orphan neurological diseases for which new drugs have been developed lately. Methods: We have conducted a literature review of the papers concerning rare diseases and their treatment, and we have analyzed the existing studies for each orphan drug. For this purpose, we have used the Google Scholar search engine and the Orphanet. We have selected the studies published in the last 15 years. Results. Since the formation of the National Organization for Rare Diseases, the Orphan Drug Act, and the National Institutes of Health Office of Rare Diseases, pharmacological companies have made a lot of progress concerning the development of new drugs. Therefore, diseases that until recently were without therapeutic solutions benefit today from personalized treatment. We have detailed in our study over 15 neurological and systemic diseases with neurological implications, for which the last 10–15 years have brought important innovations regarding their treatment. Conclusions: Many steps have been taken towards the treatment of these patients, and the humanity and professionalism of the pharmaceutical companies, along with the constant support of the patient’s associations for rare diseases, have led to the discovery of new treatments and useful future findings. Full article

(This article belongs to the Special Issue Personalized Medicine in Neurological and Neurosurgical Diseases)

14 pages, 2645 KiB

Open AccessEditor’s ChoiceReview

Should Neurosurgeons Try to Preserve Non-Traditional Brain Networks? A Systematic Review of the Neuroscientific Evidence

by Nicholas B. Dadario and Michael E. Sughrue

J. Pers. Med. 2022, 12(4), 587; https://doi.org/10.3390/jpm12040587 - 06 Apr 2022

Cited by 19 | Viewed by 3691

Abstract

The importance of large-scale brain networks in higher-order human functioning is well established in neuroscience, but has yet to deeply penetrate neurosurgical thinking due to concerns of clinical relevance. Here, we conducted the first systematic review examining the clinical importance of non-traditional, large-scale brain networks, including the default mode (DMN), central executive (CEN), salience (SN), dorsal attention (DAN), and ventral attention (VAN) networks. Studies which reported evidence of neurologic, cognitive, or emotional deficits in relation to damage or dysfunction in these networks were included. We screened 22,697 articles on PubMed, and 551 full-text articles were included and examined. Cognitive deficits were the most common symptom of network disturbances in varying amounts (36–56%), most frequently related to disruption of the DMN (n = 213) or some combination of DMN, CEN, and SN networks (n = 182). An increased proportion of motor symptoms was seen with CEN disruption (12%), and emotional (35%) or language/speech deficits (24%) with SN disruption. Disruption of the attention networks (VAN/DAN) with each other or the other networks mostly led to cognitive deficits (56%). A large body of evidence is available demonstrating the clinical importance of non-traditional, large-scale brain networks and suggests the need to preserve these networks is relevant for neurosurgical patients. Full article

(This article belongs to the Special Issue Personalized Medicine in Neurological and Neurosurgical Diseases)

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Other

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14 pages, 729 KiB

Open AccessSystematic Review

Functional Neuroimaging in Dissociative Disorders: A Systematic Review

by Martina Nicole Modesti, Ludovica Rapisarda, Gabriela Capriotti and Antonio Del Casale

J. Pers. Med. 2022, 12(9), 1405; https://doi.org/10.3390/jpm12091405 - 29 Aug 2022

Cited by 6 | Viewed by 3722

Abstract

Background: Dissociative disorders encompass loss of integration in essential functions such as memory, consciousness, perception, motor control, and identity. Nevertheless, neuroimaging studies, albeit scarce, have suggested the existence of particular brain activation patterns in patients belonging to this diagnostic category. The aim of this review is to identify the main functional neuroimaging correlates of dissociative disorders. Methods: we searched the PubMed database to identify functional neuroimaging studies conducted on subjects with a diagnosis of a dissociative disorder, following the PRISMA guidelines. In the end, we included 13 studies in this systematic review, conducted on 51 patients with dissociative identity disorder (DID), 28 subjects affected by depersonalization disorder, 24 with dissociative amnesia, and 6 with other or not specified dissociative disorders. Results: Prefrontal cortex dysfunction seems prominent. In addition, changes in the functional neural network of the caudate are related to alterations of identity state and maintenance of an altered mental status in DID. Another role in DID seems to be played by a dysfunction of the anterior cingulate gyrus. Other regions, including parietal, temporal, and insular cortices, and subcortical areas were reported to be dysfunctional in dissociative disorders. Conclusions: Prefrontal dysfunction is frequently reported in dissociative disorders. Functional changes in other cortical and subcortical areas can be correlated with these diagnoses. Further studies are needed to clarify the neurofunctional correlations of each dissociative disorder in affected patients, in order to identify better tailored treatments. Full article

(This article belongs to the Special Issue Personalized Medicine in Neurological and Neurosurgical Diseases)

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